Serum 21-deoxycortisol for diagnosis of non-classic congenital adrenal hyperplasia in women with androgen excess

Jennifer L Ng, Ee Mun Lim, Rui Zhang, John P Beilby, Gerald F Watts, Suzanne J Brown, Bronwyn G A Stuckey

Research output: Contribution to journalArticlepeer-review


PURPOSE: Non-classic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of one affected CYP21A2 allele, which currently relies on complex molecular studies. We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17OHP.

METHODS: A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a Synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by ROC analysis.

RESULTS: Basal 17OHP, stimulated 17OHP and 21DF were measured in 99, 85 and 42 participants respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L and 13.6 for stimulated 17OHP, 21DF and the ratio (21DF+17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5% and 85.0%, respectively.

CONCLUSIONS: LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.

Original languageEnglish
Pages (from-to)e1560-e1570
JournalThe Journal of clinical endocrinology and metabolism
Issue number12
Early online date26 Jun 2023
Publication statusPublished - 17 Nov 2023


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